As in the original plan, the Principal Investigator proposes to enhance the inhibitory efficiency of oligonucleotides complementary to HIV sequences, scale up the level of synthesis of the most promising molecules, and continue in vivo mouse toxicity and pharmacokinetic studies. synthesis of derivatized phosphorothioate (P-S) oligomers targeted to HIV-1 tat and gag splice/acceptor sites and evaluation of these oligomers for the ability to inhibit HIV over prolonged periods in vitro is planned. "Facilitators", oligomers which can hybridize to substrate contiguously with ribozymes and thus potentially increase their catalytic activity will be investigated. The possibility of enhancing the activity of oligomers targeted to codon initiation sites using 3' puromycin linkages will also be evaluated; other suggested oligomer modifications include 3' conjugation to streptomycin and chloramphenicol. It is further proposed that certain oligomers will be tested in vivo using a transgenic mouse developed at the Frederick Cancer Research Facility, Frederick, Maryland, which is capable of expressing BIV p24 antigen in the sera of these animals in the absence of replication- competent virus.